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Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer. The replicationdefective retroviral vector MFG was used for GM-CSF gene transfer. No dose-limiting toxicities were encountered in 16 fully evaluable patients. GM-CSF gene-transduced vaccines were equivalent in toxicity to nontransduced vaccines up to the feasible limits of autologous tumor vaccine yield. No evidence of autoimmune disease was observed. Biopsies of intradermal sites of injection with GM-CSF gene-transduced vaccines contained distinctive macrophage, dendritic cell, eosinophil, neutrophil, and T-cell infiltrates similar to those observed in preclinical models of efficacy. Histological analysis of delayed-type hypersensitivity responses in patients vaccinated 1 This work was supported by the NIH GCRC at Johns Hopkins, the Kirby Award of the Cancer Research Institute, the Longrifles Endowment, the Burroughs Wellcome Experimental Therapeutics Award, and the CaPCURE Foundation. Partial funding for this study was provided by Somatix Corporation. Under an agreement between Somatix and the Johns Hopkins University, D. P. is entitled to a share of sales royalty received by the University from Somatix. The terms of this arrangement are being managed by the University in accordance with its conflict of interest policies.

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